Based upon case reports and small case series, it has been known for many years that some types and subtypes of inherited epidermolysis bullosa (EB) may be at risk for developing one or more extracutaneous complications. Many of these are associated with considerable morbidity; some may result in death. Only over the past few years have there been data generated from large, well characterized cohorts. However, these data, to date, have been published almost exclusively in the nondermatologic literature. Our objective is to provide dermatologists with a comprehensive review of each major extracutaneous complication with a summary of the pertinent literature and recommendations for evaluation and optimal management. Part I highlights epithelial associated tissues, and part II addresses other organs. Based on these reviews, the readership should gain a greater understanding of the types of complications that may occur, when they are most likely to develop, and the range of medical and surgical interventions that are currently available. It should also be possible for the reader to develop surveillance strategies based on an understanding of the published evidence-based data. The breadth and range of severity of complications that arise in some EB types and subtypes within the external eye, ear, nose, upper airway, and gastrointestinal and genitourinary tracts suggest that optimal management must be multidisciplinary. Given the unique knowledge that dermatologists have of this disease, we believe that the care of the EB patient should be under the direction of his or her dermatologist, who can best assist in timely referrals to those specialists who are most experienced in the care of specific extracutaneous problems.